mTORC1 and mTORC2 interact with each other to regulate NK cells maturation and effector functions
作者单位：Army Medical University The Affiliated Hospital of Academy of Military Medical Sciences Soochow University University of Manitoba The Ohio State University Comprehensive Cancer Center and the James Cancer Hospital Division of HematologyDepartment of Internal MedicineThe Ohio State University
会议名称：《第十三届全国免疫学学术大会》
会议日期：2018年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学]
关 键 词：m TORC1 mTORC2 NK cell maturation effector function STAT5 SLC7A5
摘 要：The metabolic checkpoint kinase mechanistic/mammalian target of rapamycin(mTOR) plays a critical role in natural killer(NK) cell development and function, but the exact underlying mechanisms remain largely unknown. By specific depletion of Raptor(mTORC1) or Rictor(mTORC2), we found that mTORC1 and mTORC2 promoted NK cell maturation in a cooperative and non-redundant manner, mainly by controlling the expression of Tbx21 and Eomes. Intriguingly, mTORC1 and mTORC2 had opposing effects on the regulation of cytolytic function, exhibiting promoting and inhibitory effects, respectively. mTORC1 sustained mTORC2 activity by maintaining CD122-mediated IL-15 signaling, whereas mTORC2 repressed mTORC1 in controlling NK cell effector functions mainly by restraining STAT5-mediated SLC7 A5 expression. These identified mechanisms are critical for guaranteeing the proper magnitude of NK cell activation. These research findings define a previously unknown paradigm by which the interplay between mTORC1 and mTORC2 maintains the homeostasis of NK cell development and activation.